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Letters to the Editor |
1 Department of Biochemistry
3 Internal Medicine, American University of Beirut, Lebanon; The Chronic Care Center, Hazmieh, Lebanon;
2 INSERM, U770, Université Paris-Sud, Le Kremlin-Bicêtre, France; Université Louis Pasteur, Faculté de Médecine, Institut d’Hématologie et d’Immunologie, Strasbourg, France
Correspondence: Aida Habib, Department of Biochemistry, American University of Beirut, PO Box 11-236 Beirut, Lebanon. Phone: international +961.135000 ext. 4882. Fax: international +961.1370814. E-mail:ah31{at}aub.edu.lb
Patients with β-thalassemia intermedia (β TI) are completely asymptomatic until adult life, experiencing only mild anemia, maintaining hemoglobin levels between 7 and 10 g/dL, and require only occasional blood transfusions, if any. MPs are shed submicrometric plasma membrane fragments (~0.1–1 µm) harboring negatively-charged procoagulant phosphatidylserine (PS) in their extracellular membrane leaflet. They mainly derive from apoptotic or activated cells, and generally present a procoagulant potential.1 Increased levels of circulating MPs were described in many disorders with major vascular and thrombotic symptoms.2
We determined the level of circulating procoagulant MPs and their cellular origin in patients with βTI and in healthy volunteers. We prospectively included 24 patients (13 men and 11 women, mean age±SD, 29.9±8.1 years). This study was approved by the Institutional Research Board of the American University of Beirut. Among the βTI patients, 17 had splenectomy and 9 had osteoporosis. None of the patients received transfusion, and none had acute events except 2 who experienced thrombosis at least three years prior to the study. Four patients were treated daily with 100 mg of aspirin and 7 occasionally with standard doses of desferal (30–40 mg/kg/d). Hematocrit values were 28.3±5.5 (mean±SD, n=22), ranging between 21 and 38%. Ferritin concentration was 1,048±520 ng/mL, (mean±SD, n=14), ranging between 300 and 2,200 ng/mL.
Control subjects were healthy volunteers with no medication (13 men and 3 women, mean age±SD, 28.4±3.2 years). Blood was withdrawn once from patients or healthy volunteers and platelet-free plasma fractions were prepared within the first hour of blood collection. Circulating procoagulant MPs were determined using a combined assay with solid-phase annexin V-based capture and prothrombinase activity measurement as previously described.3 The cell origin of MPs was further assessed after capture onto insolubilized specific antibodies followed by measurement of prothrombinase activity. Antibodies to CD105 (R&D Systems) were used to identify MPs originating from endothelial cells, to glycoprotein (GP)Ib (a kind gift from Dr. F. Lanza, INSERM U.311, Strasbourg, France) for platelets, to CD11a (Leinco Technologies, Inc.), for leukocytes, and to glycophorin (R&D Systems) for red blood cells. Levels of MPs of patients detected by annexin V or of the different cell origins were compared with those of healthy volunteers. Statistical analysis was carried out using a statistical package for social sciences (SPSS). The level of circulating procoagulant MPs detected through binding to annexin V was elevated in βTI patients compared with healthy subjects (6.9±3.5 versus 4.7±2.9 nmol/L phosphatidylserine equivalent, mean±SD, p=0.04, independent sample t-test respectively) (Figure 1). The distribution of MP levels according to their cellular origins is also shown in this figure. Table 1 summarizes the values of circulating MPs according to their cellular origin and shows that patients have MP levels with highest statistical significance when of RBC, endothelial and leukocytic origins. A modest correlation between the MPs captured onto anti-glycophorin and anti-CD105 antibodies was observed in patients, but not in healthy volunteers (r=0.44, p<0.05, Pearson correlation). No other significant correlation was observed between the MPs of different cell origins that could characterize only the βTI patients. Platelet MPs were significantly higher in splenectomized patients versus nonsplenectomized (1.6±0.5 nmol/L phosphatidylserine equivalent, n=7, vs. 3.9±2.6, n=17 respectively p<0.001). Increase in annexin-V labeled whole RBC was previously reported in patients with β-thalassemia major (βTM) and βTI.4 It is well documented that patients with β-thalassemia have a hypercoagulable state, attributable in part to a decrease in the natural endothelial anticoagulant system, involving thrombomodulin, and proteins C and S.5 Activation of platelets and endothelium was demonstrated in ex vivo models of βTM and more recently βTI with an increase in urinary thromboxane metabolites and prostacyclin derivatives.5
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Acknowledgments
we thank Dr. Hussain Isma’eel for his help in examining the patients and monitoring the clinical data.
Footnotes
Funding: this work was performed in part with the support of the Lebanese National Center for Scientific Research (Grant # 04-08-06).
References
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